Engineered nanomaterial's have unique electrical, mechanical and physicochemical properties with potential to impact many facets of our society. However, the health and safety of nanomaterial's has recently become a major concern to the public as well as to policy makers and funding agencies. Such concern is justified in light of the vast potential for nanomaterial use in food, cosmetics, medicine, construction, bioimaging, as well as the potential exposures during manufacturing or research use. It has recently been established that nanomaterials, upon entry into a physiological environment, exhibit a tendency of physical adsorption with proteins, peptides, lipids and amino acids to render a protein corona that may influence the bioavailability and distribution of nanomaterials within the host system, at the cellular, tissue and whole organism level. Consequently, research on the health and safety implications of nanomaterials must address the following two key questions: 1) protein binding kinetics and conformational change resulting from their interaction with the nanoparticle, 2) recognition of protein corona by cellular receptors and subsequent immune responses to both the nanomaterial and the altered protein structure. The central hypothesis of this project is that the physicochemical interactions between nanomaterials and the corona components leads to changes in protein conformation, which will subsequently result in macrophage and dendritic cell activation and differential antigen presentation. We will test this hypothesis by: 1) characterizing a set of nanoparticle protein coronas; 2) determining the in vitro cellular and immune fate of nanoparticle protein corona. Understanding the impact of nanomaterial protein corona on immune response will be crucial for the development of safe nanotechnologies.